Effects of prism adaptation and visual scanning training on perceptual and response bias in unilateral spatial neglect.

In some patients with unilateral spatial neglect, symptoms reflect impaired lateralized spatial attention and representation (perceptual bias) whereas in others the inability to respond to stimuli located in contralesional space (response bias). Here, we investigated whether prismatic adaptation (PA) and visual scanning training (VST) differentially affect perceptual and response bias and whether rehabilitation outcome depends on the type of bias underlying symptoms. Two groups of neglect patients in the subacute phase were evaluated before, immediately after, and two weeks following 10 days of PA (n = 9) or VST (n = 9). Standard neuropsychological tests (i.e., Behavioural Inattentional Test, Diller cancellation test, and Line Bisection test) were administered to assess neglect symptoms, while the Landmark task was used to disentangle perceptual and response biases. Performance on the Landmark task revealed that PA was more effective in improving the perceptual bias, while VST mainly modulated the response bias. Neuropsychological tests performance suggested that VST is better suited to modulate neglect in patients with response bias, while PA may be effective in patients with both types of bias. These findings may offer novel insights into the efficacy of PA and VST in the rehabilitation of perceptual and response biases in patients with neglect.

Improvement of Impulsivity and Decision Making by Transcranial Direct Current Stimulation of the Dorsolateral Prefrontal Cortex in a Patient with Gambling Disorder.

Gambling disorder (GD) is a form of behavioral addiction. In recent years, it has been suggested that the application of transcranial Direct Current Stimulation (tDCS) to the dorsolateral prefrontal cortex (DLPFC), which plays a key role in top-down inhibitory control and impulsivity, may represent a new therapeutic approach for treating addictions. Here we investigated the effectiveness of a novel low dose tDCS protocol (i.e. six sessions of right anodal/left cathodal tDCS for 20 min, with a current intensity of 1 mA) applied to DLPFC in a patient with GD. To evaluate the effect of the proposed intervention, cognitive, psychological and behavioural evaluations were performed at different time points, pre and post intervention. The results showed improvement of impulsivity, decision making, and cognitive functioning after tDCS intervention. Findings of the present study suggest that low doses of right anodal/left cathodal tDCS to DLPFC may effectively improve gambling behaviour. They also suggest to carefully evaluate the effects of this tDCS polarity on the patient's emotional state. The current protocol warrants further investigation in large groups of patients, as it may provide relevant insights into the design of effective, low dose treatments of gambling disorder.

I'm a believer: Illusory self-generated touch elicits sensory attenuation and somatosensory evoked potentials similar to the real self-touch.

Sensory attenuation (i.e., the phenomenon whereby self-produced sensations are perceived as less intense compared to externally occurring ones) is among the neurocognitive processes that help distinguishing ourselves from others. It is thought to be rooted in the motor system (e.g., related to motor intention and prediction), while the role of body awareness, which necessarily accompanies any voluntary movement, in this phenomenon is largely unknown. To fill this gap, here we compared the perceived intensity, somatosensory evoked potentials, and alpha-band desynchronization for self-generated, other-generated, and embodied-fake-hand-generated somatosensory stimuli. We showed that sensory attenuation triggered by the own hand and by the embodied fake hand had the same behavioral and neurophysiological signatures (reduced subjective intensity, reduced of N140 and P200 SEP components and post-stimulus alpha-band desynchronization). Therefore, signals subserving body ownership influenced attenuation of somatosensory stimuli, possibly in a postdictive manner. This indicates that body ownership is crucial for distinguishing the source of the perceived sensations.

Adaptation to virtual prisms and its relevance for neglect rehabilitation: a single-blind dose-response study with healthy participants.

Prism adaptation (PA) has been applied with mixed success as a rehabilitation method of spatial neglect. Results from many single-case and multiple case studies as well as randomised controlled trials do not produce a clear picture of the efficacy of PA. We here tested a new method of PA, by inducing adaptation effects in the virtual reality. Healthy participants were attributed to one of four groups: no deviation, 10-, 20-, or 30-degrees rightward deviation. In contrast to classical wedge prisms, we induced the visual shift progressively. Participants performed two variants of the bisection and the landmark task to measure cognitive transfer of adaptation effects. Pointing error was directly related to the degree of optical deviation, and was greatest immediately following adaptation. Transfer was only observed in the bisection tasks, and only in the 30-degrees group. Due to the gradual induction of the spatial deviation the majority of participants were unaware of the adaptation effects. These findings show that large rightward deviation may affect sensorimotor performance in healthy participants similarly to neglect patients. Moreover, the finding that only participants adapted to 30-degrees showed biased bisection performance suggests that a critical threshold must be reached in order to induce significant visuomotor transfer.

Biased Visuospatial Attention in Cervical Dystonia.

OBJECTIVES: There is increasing evidence of non-motor, sensory symptoms, mainly involving the spatial domain, in cervical dystonia (CD). These manifestations are likely driven by dysfunctional overactivity of the parietal cortex during the execution of a sensory task. Few studies also suggest the possibility that visuospatial attention might be specifically affected in patients with CD. Therefore, we asked whether non-motor manifestations in CD might also comprise impairment of higher level visuospatial processing. METHODS: To this end, we investigated visuospatial attention in 23 CD patients and 12 matched healthy controls (for age, gender, education, and ocular dominance). The patients were identified according to the dystonia pattern type (laterocollis vs. torticollis). Overall, participants were right-handers, and the majority of them was right-eye dominant. Visuospatial attention was assessed using a line bisection task. Participants were asked to bisect horizontal lines, using their right or left hand. RESULTS: Participants bisected more to the left of true center when using their left hand to perform the task than when using their right hand. However, overall, torticollis patients produced a significantly greater leftward deviation than controls. CONCLUSIONS: These data are consistent with preliminary findings suggesting the presence of biased spatial attention in patients with idiopathic cervical dystonia. The presence of an attentional bias in patients with torticollis seem to indicate that alterations of attentional circuits might be implicated in the pathophysiology of this type of CD. (JINS, 2018, 24, 23-32).

Behavioral and neuroplastic effects of low-frequency rTMS of the unaffected hemisphere in a chronic stroke patient: a concomitant TMS and fMRI study.

Repetitive Transcranial Magnetic Stimulation (rTMS) ameliorates motor and neuropsychological deficits following stroke, but little is known about the underlying neuroplasticity. We investigated neuroplastic changes following 5 days of low-frequency rTMS on the intact motor cortex to promote motor recovery in a chronic patient with subcortical stroke. The feasibility of administering multiple treatments was also assessed 6 months later by applying the same protocol over the patient's parietal cortex to improve visuospatial disorders. Behavioral improvements and no adverse events were observed. Neuroimaging findings indicated that motor symptoms amelioration was associated with downregulation and cortical reorganization of hyperactive contralesional hemisphere.

Have I Been Touched? Subjective and Objective Aspects of Tactile Awareness.

Somatosensory tactile experience is a key aspect of our interaction with the environment. It is involved in object manipulation, in the planning and control of actions and, in its affective components, in the relationships with other individuals. It is also a foundational component of body awareness. An intriguing aspect of sensory perception in general and tactile perception in particular is the way in which stimulation comes to consciousness. Indeed, although being aware of something seems a rather self-evident and monolithic aspect of our mental states, sensory awareness may be in fact modulated by many different processes that impact on the mere stimulation of the skin, including the way in which we perceive our bodies as belonging to us. In this review, we first took into consideration the pathological conditions of absence of phenomenal experience of touch, in the presence of implicit processing, as initial models for understanding the neural bases of conscious tactile experience. Subsequently, we discussed cases of tactile illusions both in normal subjects and in brain-damaged patients which help to understand which high-order processes impact tactile awareness. Finally, we discussed the observations reported in the review in light of some influential models of touch and body representation.

Medial anterior prefrontal cortex stimulation downregulates implicit reactions to threats and prevents the return of fear.

Downregulating emotional overreactions toward threats is fundamental for developing treatments for anxiety and post-traumatic disorders. The prefrontal cortex (PFC) is critical for top-down modulatory processes, and despite previous studies adopting repetitive transcranial magnetic stimulation (rTMS) over this region provided encouraging results in enhancing extinction, no studies have hitherto explored the effects of stimulating the medial anterior PFC (aPFC, encompassing the Brodmann area 10) on threat memory and generalization. Here we showed that rTMS over the aPFC applied before threat memory retrieval immediately decreases implicit reactions to learned and novel stimuli in humans. These effects enduringly persisted 1 week later in the absence of rTMS. No effects were detected on explicit recognition. Critically, rTMS over the aPFC resulted in a more pronounced reduction of defensive responses compared to rTMS targeting the dorsolateral PFC. These findings reveal a previously unexplored prefrontal region, the modulation of which can efficiently and durably inhibit implicit reactions to learned threats. This represents a significant advancement toward the long-term deactivation of exaggerated responses to threats.

Contribution of rat intestinal metabolism to the xenobiotics clearance.

Michaelis-Menten constants K m and V max values were determined by product formation and substrate depletion at several substrate concentrations of 4-methylumbelliferone using rat intestinal microsomes. K m and V max values determined by measuring product formation were in good agreement with substrate depletion approach. We also investigated hepatic and intestinal in vitro intrinsic clearance (CLint) in the liver and intestinal microsomes and compare with reports in the literature using nine test compounds, atorvastatin, 7-ethoxycoumarin, indomethacin, 4-methylumbelliferone, midazolam, nifedipine, testosterone, terfenadine and verapamil, in rats. CLint was determined from the substrate disappearance rate at 0.1 and 0.5 µM in the rat intestinal and liver microsomes, respectively. These results showed that both the liver and the intestine contributed to the metabolism of these compounds. The intestinal intrinsic clearance values of all these drugs, except for terfenadine in the rat intestinal microsomes, were lower than their hepatic intrinsic clearance per milligram protein, showing that there was an organ difference in metabolism between the liver and intestinal. These results make the evaluation using the intestinal more useful and provide a basis for predicting clearance using intestinal.

Modulation of Motor Awareness: A Transcranial Magnetic Stimulation Study in the Healthy Brain.

Previous studies on the mechanisms underlying willed actions reported that the premotor cortex may be involved in the construction of motor awareness. However, its exact role is still under investigation. Here, we investigated the role of the dorsal premotor cortex (PMd) in motor awareness by modulating its activity applying inhibitory rTMS to PMd, before a specific motor awareness task (under three conditions: without stimulation, after rTMS and after Sham stimulation). During the task, subjects had to trace straight lines to a given target, receiving visual feedback of the line trajectories on a computer screen. Crucially, in most trials, the trajectories on the screen were deviated, and to produce straight lines, subjects had to correct their movements towards the opposite direction. After each trial, participants were asked to judge whether the line seen on the computer screen corresponded to the line actually drawn. Results show that participants in the No Stimulation condition did not recognize the perturbation until 14 degrees of deviation. Importantly, active, but not Sham, rTMS significantly modulated motor awareness, decreasing the amplitude of the angle at which participants became aware of the trajectory correction. These results suggest that PMd plays a crucial role in action self-monitoring.

Can static Rorschach stimuli perceived as in motion affect corticospinal excitability?

It has been proposed that seeing human movement or activity (M), while trying to say what the static Rorschach inkblot design look like, is accompanied by Mirror Neuron System (MNS)-like mirroring activity in the brain. The present study aimed to investigate whether the Rorschach cards eliciting M responses could affect the excitability of the motor cortex by recording motor evoked potentials (MEPs) elicited by single-pulse TMS over the primary motor cortex (M1). We hypothesized that Rorschach inkblot stimuli triggering the viewer's experience of human movement would increase corticospinal excitability. Twenty-one healthy volunteers (15 women) participated in the preliminary experiment, while another different sample of twenty-two healthy participants (11 women) ranging in age from 21 to 41 years was enrolled in the main experiment. Our results showed that the Rorschach cards known to be associated with a high number of M responses elicited human movement both as automatic internal sensations and as verbal production of responses involving human movement. However, contrary to our hypothesis, the reported internal feeling of human movement had no corresponding physiological counterpart, as the amplitude of MEPs did not increase. Possible and innovative explanations for the involvement of bottom-up and top-down processes were provided.

Modulation of vestibular input by short-term head-down bed rest affects somatosensory perception: implications for space missions.

Introduction: On Earth, self-produced somatosensory stimuli are typically perceived as less intense than externally generated stimuli of the same intensity, a phenomenon referred to as somatosensory attenuation (SA). Although this phenomenon arises from the integration of multisensory signals, the specific contribution of the vestibular system and the sense of gravity to somatosensory cognition underlying distinction between self-generated and externally generated sensations remains largely unknown. Here, we investigated whether temporary modulation of the gravitational input by head-down tilt bed rest (HDBR)-a well-known Earth-based analog of microgravity-might significantly affect somatosensory perception of self- and externally generated stimuli. Methods: In this study, 40 healthy participants were tested using short-term HDBR. Participants received a total of 40 non-painful self- and others generated electrical stimuli (20 self- and 20 other-generated stimuli) in an upright and HDBR position while blindfolded. After each stimulus, they were asked to rate the perceived intensity of the stimulation on a Likert scale. Results: Somatosensory stimulations were perceived as significantly less intense during HDBR compared to upright position, regardless of the agent administering the stimulus. In addition, the magnitude of SA in upright position was negatively correlated with the participants' somatosensory threshold. Based on the direction of SA in the upright position, participants were divided in two subgroups. In the subgroup experiencing SA, the intensity rating of stimulations generated by others decreased significantly during HDBR, leading to the disappearance of the phenomenon of SA. In the second subgroup, on the other hand, reversed SA was not affected by HDBR. Conclusion: Modulation of the gravitational input by HDBR produced underestimation of somatosensory stimuli. Furthermore, in participants experiencing SA, the reduction of vestibular inputs by HDBR led to the disappearance of the SA phenomenon. These findings provide new insights into the role of the gravitational input in somatosensory perception and have important implications for astronauts who are exposed to weightlessness during space missions.

Beyond alpha-band: The neural correlate of creative thinking.

The compound nature of creativity entails the interplay of multiple cognitive processes, making it difficult to attribute creativity to a single neural signature. Divergent thinking paradigms, widely adopted to investigate creative production, have highlighted the key role of specific mental operations subserving creativity, such as inhibition of external stimuli, loose semantic associations, and mental imagery. Neurophysiological studies have typically shown a high alpha rhythm synchronization when individuals are engaged in creative ideation. Also, oculomotor activity and pupil diameter have been proposed as useful indicators of mental operations involved in such a thinking process. The goal of this study was to investigate whether beyond alpha-band activity other higher frequency bands, such as beta and gamma, may subserve divergent and convergent thinking and whether those could be associated with a different gaze bias and pupil response during ideas generation. Implementing a within-subjects design we collected behavioral measures, neural activity, gaze patterns, and pupil dilation while participants performed a revised version of the Alternative Uses Task, in which divergent thinking is contrasted to convergent thinking. As expected, participants took longer to generate creative ideas as compared to common ones. Interestingly, during divergent thinking participants displayed alpha synchronization along with beta and gamma desynchronization, more pronounced leftward gaze shift, and greater pupil dilation. During convergent thinking, an opposite pattern was observed: desynchronization in alpha and an increase in beta and gamma rhythm, along with a reduction of leftward gaze shift and greater pupil constriction. The present study uncovered specific neural dynamics and physiological patterns during idea generation, providing novel insight into the complex physiological signature of creative production.

Virtual reality rehabilitation for unilateral spatial neglect: A systematic review of immersive, semi-immersive and non-immersive techniques.

INTRODUCTION: In recent decades, new virtual reality (VR)-based protocols have been proposed for the rehabilitation of Unilateral Spatial Neglect (USN), a debilitating disorder of spatial awareness. However, it remains unclear which type of VR protocol and level of VR immersion can maximize the clinical benefits. To answer these questions, we conducted a systematic review of the use of VR for the rehabilitation of USN. METHOD: Studies between 2000 and 2022 that met the inclusion criteria were classified according to their research design and degree of immersion (non-immersive, NIVR; semi-immersive, SIVR; immersive, IVR). RESULTS: A total of 375 studies were identified, of which 26 met the inclusion criteria. Improvements were found in 84.6% of the reviewed studies: 85.7% used NIVR, 100% used SIVR and 55.6% used IVR. However, only 42.3% of them included a control group and only 19.2% were randomized control trials (RCT). CONCLUSION: VR protocols may offer new opportunities for USN rehabilitation, although further RCTs are needed to validate their clinical efficacy.

Formaldehyde and Acetaldehyde Exposure in "Non-Traditional" Occupational Sectors: Bakeries and Pastry Producers.

INTRODUCTION: Formaldehyde, a colorless and highly irritating substance, causes cancer of the nasopharynx and leukemia. Furthermore, it is one of the environmental mutagens to which humans are most abundantly exposed. Acetaldehyde was recently classified as carcinogen class 1B and mutagen class 2 in Annex VI EC regulation. Occupational exposure to the two aldehydes occurs in a wide variety of occupations and industries. The aim of this study is to deepen exposure to the two aldehydes in the non-traditional productive sectors of bakeries and pastry producers. METHODS: The evaluation of exposure to formaldehyde and acetaldehyde was conducted in Italy in 2019, in specific tasks and positions of 11 bakeries and pastry producers (115 measures, of which 57.4% were in fixed positions and the rest were personal air sampling). The measurements were performed using Radiello© radial diffusion samplers. A logarithmic transformation of the data was performed, and the correlation between the two substances was calculated. Moreover, linear models considering the log-formaldehyde as the outcome and adjusting for log-acetaldehyde values were used. RESULTS: The study identified high levels of acetaldehyde and formaldehyde exposure in the monitored workplaces. Higher mean values were observed in the leavening phase (8.39 µg/m3 and 3.39 µg/m3 for log-transformed data acetaldehyde and formaldehyde, respectively). The adjusted univariate analyses show statistically significant factors for formaldehyde as the presence of yeast, the presence of type 1 flour, the use of barley, the use of fats, the type of production, the use of spelt, and the presence of type 0 flour. CONCLUSIONS: The measurements confirmed the release of formaldehyde and acetaldehyde in bakeries and pastry industries, especially in some phases of the work process, such as leavening.

The Oppel-Kundt illusion is effective in modulating horizontal space representation in humans.

A modified version of the Oppel-Kundt illusion (i.e., a filled space is perceived as more expanded than an empty space of the same length) has been previously employed to distort space representation both in patients with neglect (i.e., failure to report/react to stimuli located in the space contralateral to the brain lesion) and in healthy participants. In those experiments, participants had to bisect or extend horizontal segments on backgrounds of exponentially spaced vertical lines. The exclusive use of visuo-motor tasks, however, did not allow excluding that the results were accounted for by a bias occurring at a response level of stimulus processing rather than by a visual illusion. To address this issue, in addition to a traditional line bisection task, a line length estimation task was employed, which allowed separating response and illusion-related factors. The results demonstrated that performance depended on the visual illusion rather than on a response bias. It was concluded that this version of the Oppel-Kundt illusion can be successfully employed to modulate space representation in humans.

Nice and easy: Mismatch negativity responses reveal a significant correlation between aesthetic appreciation and perceptual learning.

Neurocomputational models of cognition have framed aesthetic appreciation within the domain of knowledge acquisition and learning, suggesting that aesthetic appreciation might be considered as a hedonic feedback on successful perceptual learning dynamics. Such hypothesis, however, has never been empirically demonstrated yet. In order to investigate the relationship between aesthetic appreciation and learning, we measured the EEG mismatch negativity (MMN) response to more or less appreciated musical intervals, which is considered as a reliable index of perceptual learning. To this end, we measured the MMN to frequency (Hz) standard and frequency deviant musical intervals (Experiment 1) while participants were asked to judge their beauty. For each single stimulus, we also computed an information-theoretic index of perceptual learning (Bayesian surprise). We found that more appreciated musical intervals were associated with a larger MMN responses, which, in turn, correlated with trial-by-trial fluctuations in Bayesian surprise (Experiment 1). Coherently with previous results, Bayesian surprise was also found to correlate with slower RTs in a detection task of the same stimuli, evidencing that motor behavior is inhibited in presence of surprising sensory states triggering perceptual learning (Experiment 2). Our results provide empirical evidence of the existence of a positive correlation between aesthetic appreciation and EEG indexes of perceptual learning. We argue that the sense of beauty might have evolved to signal the nervous system new sensory knowledge acquisition and motivate the individual to search for informationally profitable stimuli. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Using interleaved transcranial magnetic stimulation/functional magnetic resonance imaging (fMRI) and dynamic causal modeling to understand the discrete circuit specific changes of medications: lamotrigine and valproic acid changes in motor or prefrontal effective connectivity.

The purpose of this study was to use interleaved transcranial magnetic stimulation/functional magnetic resonance imaging (TMS/fMRI) to investigate the effects of lamotrigine (LTG) and valproic acid (VPA) on effective connectivity within motor and corticolimbic circuits. In this randomized, double-blind, crossover trial, 30 healthy volunteers received either drug or placebo 3.5 h prior to interleaved TMS/fMRI. We utilized dynamic causal modeling (DCM) to assess changes in the endogenous effective connectivity of bidirectional networks in the motor-sensory system and corticolimbic circuit. Results indicate that both LTG and VPA have network-specific effects. When TMS was applied over the motor cortex, both LTG and VPA reduced TMS-specific effective connectivity between primary motor (M1) and pre-motor cortex (PMd), and between M1 and the supplementary area motor (SMA). When TMS was applied over prefrontal cortex, however, LTG alone increased TMS-specific effective connectivity between the left dorsolateral prefrontal cortex(DLPFC) and the anterior cingulate cortex (ACC). In summary, LTG and VPA inhibited effective connectivity in motor circuits, but LTG alone increased effective connectivity in prefrontal circuits. These results suggest that interleaved TMS/fMRI can assess region- and circuit-specific effects of medications or interventions.

When Right Goes Left: Phantom Touch Induced by Mirror Box Procedure in Healthy Individuals.

In the present article, we investigated the possibility of inducing phantom tactile sensations in healthy individuals similar to those that we observed in patients after stroke. On the basis of previous research, we assumed that manipulating visual feedbacks may guide and influence, under certain conditions, the phenomenal experience of touch. To this aim, we used the Tactile Quadrant Stimulation (TQS) test in which subjects, in the crucial condition, must indicate whether and where they perceive a double tactile stimulation applied simultaneously in different quadrants of the two hands (asymmetrical Double Simultaneous Stimulation trial, Asym-DSS). The task was performed with the left-hand out of sight and the right-hand reflected in a mirror so that the right-hand reflected in the mirror looks like the own left-hand. We found that in the Asym-DSS trial, the vision of the right-hand reflected in the mirror and stimulated by a tactile stimulus elicited on the left-hand the sensation of having been touched in the same quadrant as the right-hand. In other words, we found in healthy subjects the same phantom touch effect that we previously found in patients. We interpreted these results as modulation of tactile representation by bottom-up (multisensory integration of stimuli coming from the right real and the right reflected hand) and possibly top-down (body ownership distortion) processing triggered by our experimental setup, unveiling bilateral representation of touch.